TY - JOUR
T1 - β-endorphin-induced feeding
T2 - Pharmacological characterization using selective opioid antagonists and antisense probes in rats
AU - Silva, Robert M.
AU - Hadjimarkou, Maria M.
AU - Rossi, Grace C.
AU - Pasternak, Gavril W.
AU - Bodnar, Richard J.
PY - 2001
Y1 - 2001
N2 - Ventricular administration of the opioid βEND induces feeding in rats. Since its pharmacological characterization has not been fully identified, the present study examined whether equimolar doses of general and selective opioid antagonists as well as AS ODN opioid probes altered spontaneous daytime feeding over a 4-h time course elicited by βEND. βEND-induced feeding was significantly reduced by moderate (20-40-nmol, i.c.v.) doses of general (naltrexone) opioid antagonists, and lower (0.5-40-nmol) doses of selective μ (β-funaltrexamine)-antagonists. Correspondingly, AS ODN probes directed against either exons 1, 3, or 4, but not exon 2, of the μ-opioid receptor clone reduced βEND-induced feeding; a missense ODN control probe was ineffective. The δ-antagonist Nti (20-40 nmol) reduced βEND-induced feeding to a lesser degree, and AS ODN probes targeting exon 1, but not 2 or 3, of the δ-opioid receptor clone significantly reduced βEND-induced feeding. Although the selective κ1-receptor antagonist NBNI (20-40 nmol) significantly reduced βEND-induced feeding, this response was not altered by AS ODN probes directed against either exons 1, 2, or 3 of either the KOR-1 clone or the κ3-like opioid receptor clone. These converging antagonist and AS ODN data firmly implicate the μ-opioid receptor in the mediation of βEND-induced feeding. The relative lack of convergence between the lesser effectiveness of Nti and NBNI in reducing βEND-induced feeding, and the lack of effectiveness of their corresponding AS ODN probes suggest that δ- and κ-receptors play a minimal role in the mediation of this response.
AB - Ventricular administration of the opioid βEND induces feeding in rats. Since its pharmacological characterization has not been fully identified, the present study examined whether equimolar doses of general and selective opioid antagonists as well as AS ODN opioid probes altered spontaneous daytime feeding over a 4-h time course elicited by βEND. βEND-induced feeding was significantly reduced by moderate (20-40-nmol, i.c.v.) doses of general (naltrexone) opioid antagonists, and lower (0.5-40-nmol) doses of selective μ (β-funaltrexamine)-antagonists. Correspondingly, AS ODN probes directed against either exons 1, 3, or 4, but not exon 2, of the μ-opioid receptor clone reduced βEND-induced feeding; a missense ODN control probe was ineffective. The δ-antagonist Nti (20-40 nmol) reduced βEND-induced feeding to a lesser degree, and AS ODN probes targeting exon 1, but not 2 or 3, of the δ-opioid receptor clone significantly reduced βEND-induced feeding. Although the selective κ1-receptor antagonist NBNI (20-40 nmol) significantly reduced βEND-induced feeding, this response was not altered by AS ODN probes directed against either exons 1, 2, or 3 of either the KOR-1 clone or the κ3-like opioid receptor clone. These converging antagonist and AS ODN data firmly implicate the μ-opioid receptor in the mediation of βEND-induced feeding. The relative lack of convergence between the lesser effectiveness of Nti and NBNI in reducing βEND-induced feeding, and the lack of effectiveness of their corresponding AS ODN probes suggest that δ- and κ-receptors play a minimal role in the mediation of this response.
UR - http://www.scopus.com/inward/record.url?scp=0035038503&partnerID=8YFLogxK
M3 - Article
C2 - 11303047
AN - SCOPUS:0035038503
SN - 0022-3565
VL - 297
SP - 590
EP - 596
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
IS - 2
ER -